MMTV-Id-1형질전환 마우스 모델에서 Id-1의 유선 발달에 관한 기능 연구
- Title
- MMTV-Id-1형질전환 마우스 모델에서 Id-1의 유선 발달에 관한 기능 연구
- Other Titles
- The Role of Id-1 in Mammary Gland Development of MMTV-Id-1 Transgenic Mouse
- Author
- 신동희
- Advisor(s)
- 공구
- Issue Date
- 2011-02
- Publisher
- 한양대학교
- Degree
- Doctor
- Abstract
- Inhibitor of differentiation-1 (Id-1) has been shown to play an essential role in cell proliferation, invasion, migration and anti-apoptosis. However, the effect of Id-1 in mammary gland development in in vivo remains unknown. Here, we analyzed the effect of Id-1 overexpression in mammary gland development of MMTV-Id-1 transgenic mice during virgin, pregnancy and involution. In virgin mice, overexpression of Id-1 led to precocious development and delayed regression of terminal end buds (TEBs) compared with wild type mice. The number of BrdU-positive cells, an indicator of cell proliferation, and the expression of Wnt signaling molecules, β-catenin and cyclin D1, which regulate ductal extension and TEB formation in virgin, were statistically higher in Id-1 transgenic mice than in wild type mice. Id-1 also had an effect on the formation and proliferation of lobuloalveolar structures during early and mid-pregnancy. The Id-1 transgenic mice had more lobulated and prominent alveolar budding than wild type mice and had significantly greater counts of lobuloalveolar structures in early pregnancy. The expression of BrdU, β-catenin and cyclin D1 was also predominantly increased in Id-1 transgenic mice. Moreover, Id-1 transgenic mice showed delayed involution in mammary gland development. Id-1 regulated the expression levels of anti-apoptotic Bcl-2 and pro-apoptotic Bax, and resulted in delay of apoptotic peak during postlactational involution. We also investigated whether Id-1 is able to modulate activity of the Wnt/β-catenin signaling pathway throughout Retinoic acid, FGF, TGFβ, and BMP pathways in tubuloalveolar development of mammary glands. Akt phosphorylation, BMP2, FGF3 and RAR-β were dysregulated by constitutive overexpression of Id-1 in the proliferation of mammary glands. Taken together, our results suggest that Id-1 plays a pivotal role in mammary gland development through Wnt signaling-mediated acceleration of precocity and alveologenesis and Bcl-2 family members-mediated delay of involution.
- URI
- https://repository.hanyang.ac.kr/handle/20.500.11754/140199http://hanyang.dcollection.net/common/orgView/200000415863
- Appears in Collections:
- GRADUATE SCHOOL[S](대학원) > DEPARTMENT OF BIOMEDICAL SCIENCES(의생명공학과) > Theses (Ph.D.)
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